N-bromobutanimide → N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]phenyl}-2,5-difluorobenzenesulfonamide

HRID 1961802Notes

Reaction equation

HRID 1961802 reaction equation
[Cl:1][C:2]1[C:7](/[C:8](/O)=[CH:9]\[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:16])[N:11]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:18][S:19]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[F:29])(=[O:21])=[O:20].C1C(=O)N(Br)C(=O)C1.[CH3:38][C:39]([CH3:44])([CH3:43])[C:40](=[S:42])[NH2:41]>CC(N(C)C)=O.CCOC(C)=O>[Cl:1][C:2]1[C:7]([C:8]2[N:41]=[C:40]([C:39]([CH3:44])([CH3:43])[CH3:38])[S:42][C:9]=2[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:16])[N:11]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:18][S:19]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[F:29])(=[O:21])=[O:20]

Participants

6

Reactant 3

HCID 67184N-bromobutanimideHCID 30311302,2-DimethylpropanethioamideHCID 136342907N-{2-Chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,5-difluorobenzenesulfonamide

Product 1

HCID 57989680N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]phenyl}-2,5-difluorobenzenesulfonamideYield 36%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{2-chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,5-difluorobenzenesulfonamide (3.0 g, 6.55 mmol) in DMA (25 mL) was added NBS (1.165 g, 6.55 mmol). After stirring for 1 h at rt, 2,2-dimethylpropanethioamide (0.767 g, 6.55 mmol) was added and the reaction mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with EtOAc (100 mL) and extracted five times with water. The organic layer was dried over anhydrous NaSO4, adsorbed onto silica gel, and purified via column chromatography, eluting with 0-50% EtOAc/DCM. The desired fractions were combined and concentrated to generate 1.31 g (2.36 mmol, 36.0% yield) of the title compound as a yellow powder. 1H NMR (400 MHz, DMSO-d6): δ 10.74 (s, 1H), 8.56 (d, J=5.4 Hz, 1H), 7.41-7.58 (m, 6H), 6.57 (d, J=5.4 Hz, 1H), 1.42 (s, 9H). MS (ESI): 555.0 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at 80° C. for 2 h
  2. extractionextracted five times with water
  3. dry with materialThe organic layer was dried over anhydrous NaSO4
  4. custompurified via column chromatography
  5. washeluting with 0-50% EtOAc/DCM
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3708bbadc2dd476a84048025d6b0f58e
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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